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Endothelin-Converting Enzyme-1 Is Expressed on Human Ovarian Follicles and Corpora Lutea of Menstrual Cycle and Early Pregnancy¹

Department of Gynecology and Obstetrics, Faculty of Medicine (S.Yo., H.F., S.Ya., K.T., T.N., T.H., T.I., S.F.), and Institute for Frontier Medical Science (M.M.), Kyoto University, Sakyo-ku, Kyoto, 606, Japan

Address all correspondence and requests for reprints to: Hiroshi Fujiwara, M.D., Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan. E mail: fuji@kuhp.kyoto-u.ac.jp.

We have previously reported that membrane-bound amino- and carboxypeptidases were expressed on the human follicles and corpora lutea (CL), and we proposed that these peptidases are involved in ovarian functions, probably by regulating the extracellular peptide concentrations. In this study, we examined the expression of endothelin-converting enzyme-1 (ECE-1) on human follicles and CL, which is a membrane-bound endopeptidase and is known to convert big endothelin-1 to endothelin-1.

In the preovulatory follicles, immunohistochemical study showed that ECE-1 was expressed, with moderate intensity, on the theca interna cells and weakly on the granulosa cells. In the menstrual and pregnant CL, ECE-1 was highly expressed on both large and small luteal cells, indicating that ECE-1 expression increases during luteinization. Western blotting analysis revealed that the molecular mass of the ECE-1 extracted from the menstrual CL was 130 kDa and that ECE-1 was more strongly expressed on the CL in early and midluteal phases than the CL in late luteal phases. In the isolated luteinizing granulosa cells obtained from patients undergoing in vitro fertilization, ECE-1 was immunohistochemically detected on their cell surface. The activity of ECE-1 was also detected on cultured luteinizing granulosa cells by measuring endothelin-1 production from its precursor. The activity of ECE-1 was significantly enhanced by the treatment of human CG (10 U/mL) and interleukin (IL)-1 (10 ng/mL) during 4-day culture, whereas no significant alteration was observed by IL-4 (10 ng/mL) and IL-10 (10 ng/mL) treatment.

These results indicate that ECE-1 is a cell surface differentiation-related molecule of human granulosa and of theca interna cells and suggest that the expression of ECE-1 is regulated by LH/human CG and cytokines.

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